INDUCTION OF GENE AMPLIFICATION BY ARSENIC
INDUCTION OF GENE AMPLIFICATION BY ARSENIC
复制标题
DOI：
10.1126/science.3388020
复制
发表时间：
1988-07-01
期刊：
影响因子：
56.9
通讯作者：
BARRETT, JC
中科院分区：
文献类型：
--
作者：
LEE, TC;TANAKA, N;BARRETT, JC
砷是一种公认的人类致癌物，但几乎没有证据表明其在动物中的致癌性，并且在小鼠致癌性的两阶段模型中作为引发剂或肿瘤促进剂是无活性的。两种砷盐（亚砷酸钠和砷酸钠）诱导了高频率的甲氨蝶呤耐药3T6细胞，这被证明具有扩增的二氢叶酸还原酶基因的拷贝。砷诱导基因扩增的能力可能与其在人类中的致癌作用有关，因为在许多人类肿瘤中观察到癌基因扩增。砷不能诱导基因突变可能与砷在长期动物研究中的负面结果有关，并表明这些实验可能无法检测到一些在人类致癌过程后期起作用的环境因子。
Arsenic is a well-established carcinogen in humans, but there is little evidence for its carcinogenicity in animals and it is inactive as an initiator or tumor promoter in two-stage models of carcinogenicity in mice. Two arsenic salts (sodium arsenite and sodium arsenate) induced a high frequency of methotrexate-resistant 3T6 cells, which were shown to have amplified copies of the dihydrofolate reductase gene. The ability of arsenic to induce gene amplification may relate to its carcinogenic effects in humans since amplification of oncogenes is observed in many human tumors. The inability of arsenic to induce gene mutations may relate to the negative results of arsenic in long-term animal studies and suggests that these experiments may not detect some environmental agents that act late in the carcinogenic process in humans.